chr1-226363223-G-C

Position:

• chr1-226363223-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001618.4(PARP1):​c.2787-63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,072,544 control chromosomes in the GnomAD database, including 214,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26425 hom., cov: 32)
  • Exomes 𝑓: 0.63 (187618 hom.)
• Consequence: PARP1 NM_001618.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616

Genes affected

PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4	c.2787-63C>G		intron_variant		ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10	c.2787-63C>G		intron_variant		1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87768 AN: 151954 Hom.: 26426 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.629 AC: 578578 AN: 920472 Hom.: 187618 AF XY: 0.632 AC XY: 304304 AN XY: 481414

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.577 AC: 87799 AN: 152072 Hom.: 26425 Cov.: 32 AF XY: 0.573 AC XY: 42630 AN XY: 74338

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.606

Alfa AF: 0.625 Hom.: 3770

Bravo AF: 0.563

Asia WGS AF: 0.459 AC: 1597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.47
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs747657; hg19: chr1-226550924; COSMIC: COSV64690496; COSMIC: COSV64690496;